Findings reveal that deficiency of the SMN protein in peripheral tissues might also contribute to SMA pathology

Cold Spring Harbor, N.Y. – A new study from Cold Spring Harbor Laboratory (CSHL) reports surprising results that suggest that the devastating neuromuscular disease, spinal muscular atrophy (SMA), might not exclusively affect the motor neurons in the spinal cord as has long been thought. The new findings suggest that defects in peripheral tissues such as liver, muscle, heart, etc., might also contribute to the pathology of the disease in severely affected patients. The study, which also paves the way for a potential SMA drug to enter human trials by the end of the year, appears in Nature on October 6.

These insights stem from experiments that tested the new candidate drug, which the CSHL scientists helped develop, in a mouse model of very severe SMA. In this system, the candidate drug dramatically suppressed symptoms when simply injected under the animals’ skin. “These systemic, or subcutaneous, injections, extended the lifespan of mice that have the equivalent of severe human SMA by 25-fold,” reports CSHL’s Professor Adrian Krainer, Ph.D., who led the CSHL team in collaboration with a group led by Dr. Frank Bennett of California-based Isis Pharmaceuticals.

“However, we have yet to determine whether these findings are unique to this animal model of severe SMA—and by extension, relevant only to the patients with the most severe disease —or if they will be valid in other SMA types that manifest with milder, less severe symptoms,” cautions Dr. Bennett.